FDA Grants Priority Review for Glofitamab for Blood Cancer

The FDA has accepted Genentech’s biologics license application (BLA) and granted priority review for glofitamab to treat adult patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. Large B-cell lymphoma is a fast-growing non-Hodgkin’s lymphoma (NHL) and is one of the most prevalent types of blood cancer among adults in the United States.

Glofitamab is a T-cell engaging bispecific antibody that targets CD3 on the surface of T cells and CD20 on the surface of B cells. It was engineered to have one region that binds to CD3, a protein on T cells, and two regions that bind to CD20, a protein on B cell. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell.

If approved, it would be the first off-the-shelf T-cell engaging bispecific antibody to treat people with an aggressive lymphoma who have previously received multiple courses of treatment. The FDA is expected to make a decision on approval by July 1, 2023.

Levi Garraway, M.D., Ph.D.

“Unfortunately, people with relapsed or refractory large B-cell lymphoma have a poor prognosis and desperately need additional therapies that are immediately available at the time of relapse,” Levi Garraway, M.D., Ph.D., chief medical officer and head of global product development of Genentech, said in a press release.

The submission is based on positive data from the pivotal phase 1/2 NP30179 study, which included patients who had previously received multiple courses of therapy. Results showed that 40.0% of patients achieved a complete response (CR), which was defined as a disappearance of all signs of cancer, and 51.6% achieved an objective response (OR), which was defined as the combination of a complete response and partial response, a decrease in the amount of cancer in their body. The median follow-up time was 13.4 months. Among those who achieved a complete response, 73.1% continued to experience a response at 12 months. The median duration of response was 18.4 months.

The most common adverse event was cytokine release syndrome, which was generally low grade. The incidence of grade 3 or higher cytokine release syndrome was 3.9%, with no grade 5 events. Only one patient discontinued glofitamab due because of cytokine release syndrome.

Research of glofitamab is ongoing. It is being studied in combination with gemcitabine and oxaliplatin (GemOx) versus rituximab in combination with GemOx in patients with second-line plus diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant. Additional studies are ongoing to investigate the molecule as a monotherapy and in combination with other medicines for the treatment of patients with B-cell non-Hodgkin’s lymphomas, including DLBCL, mantle cell lymphoma and other blood cancers.

Related: FDA Approves First Bispecific Antibody for Follicular Lymphoma

Glofitamab is part of Genentech’s CD20xCD3 T-cell engaging bispecific antibody clinical program. Last month, the FDA issued an accelerated approval for another Genentech bispecific antibody: Lunsumio (mosunetuzumab-axgb) to treat adult patients with relapsed or refractory (R/R) follicular lymphoma (FL). It is indicated for patients after two or more lines of systemic therapy.